Polymer Stiffness Regulates Multivalent Binding and Liquid-Liquid Phase Separation
Name
Polymer_Stiffness_Regulates_Multivalent_Binding_an.pdf
Description
Accepted version
Size
2.07 MB
Format
Adobe PDF
Checksum (MD5)
002db432c69d48d6ee3ff046e4baec17
Author(s)
Zumbro, Emiko
Alexander-Katz, Alfredo
Date Issued
2020
Journal
Biophysical Journal
Publisher
Elsevier BV
Citation
Zumbro, Emiko and Alexander-Katz, Alfredo. 2020. "Polymer Stiffness Regulates Multivalent Binding and Liquid-Liquid Phase Separation." Biophysical Journal, 119 (9).
Version
Author's final manuscript
Abstract
© 2020 Biophysical Society Multivalent binding is essential to many biological processes because it builds high-affinity bonds by using several weak binding interactions simultaneously. Multivalent polymers have shown promise as inhibitors of toxins and other pathogens, and they are important components in the formation of biocondensates. Explaining how structural features of these polymers change their binding and subsequent control of phase separation is critical to designing better pathogen inhibitors and also to understanding diseases associated with membraneless organelles. In this work, we will examine the binding of a multivalent polymer to a small target. This scenario could represent a polymeric inhibitor binding to a toxic protein or RNA binding to an RNA-binding protein in the case of liquid-liquid phase separation. We use simulation and theory to show that flexible random-coil polymers bind more strongly than stiff rod-like polymers and that flexible polymers nucleate condensed phases at lower binding energies than their rigid analogs. We hope these results will provide insight into the rational design of polymeric inhibitors and improve our understanding of phase separation in cells and membraneless organelles.
MIT Department
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licens
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.BPJ.2020.09.035
